P1011: PREDICTORS OF COVID-19 DISEASE AND SURVIVAL TO COVID-19 IN MPN PATIENTS TREATED WITH RUXOLITINIB
Authors: F. Palandri, D. Bartoletti, E. M. Elli, G. Auteri, M. Bonifacio, G. Benevolo, F. Heidel, M. M. Trawinska, E. Rossi, C. Bosi, A. Tieghi, M. Tiribelli, A. Iurlo, N. Polverelli, G. Caocci, G. Binotto, F. Cavazzini, E. Beggiato, D. Cilloni, C. Tatarelli, F. Mendicino, M. Miglino, M. Bocchia, M. Crugnola, C. Mazzoni, A. D. Romagnoli, G. Rindone, S. Ceglie, A. D’Addio, E. Santoni, D. Cattaneo, R. M. Lemoli, M. Krampera, A. Cuneo, G. Semenzato, R. Latagliata, E. Abruzzese, N. Vianelli, M. Cavo, A. Andriani, V. De Stefano, G. Palumbo, M. Breccia
Journal: HemaSphere (2022)

Background: Ruxolitinib (RUX) use and discontinuation are risk factors for severe COVID-19 and death in MPN patients (pts). In pts on RUX therapy, predictors for COVID-19 disease and survival (OS) to COVID-19 are unknown. Aims: The aims of this study were to distinguish RUX-treated pts at higher risk of COVID-19 and to assess prognostic factors for OS. Methods: We performed a sub-analysis of the RUX-MF and the PV-ARC observational studies that include consecutive adult pts with myelofibrosis (MF) and polycythemia vera (PV), respectively. Overall, 815 MF and 172 PV pts treated with RUX outside clinical trials have been registered. At pandemic start, 494 pts (359 MF and 135 PV) on RUX were included in this analysis. Results: Among 66 (13.6%) pts (PV n=11, MF n=55) with COVID-19 from Feb 2020 to Jan 2022, 1 (1.5%), 14 (21.2%), 9 (13.6%), 17 (25.8%), 4 (6.1%) and 21 (31.8%) pts had an asymptomatic, mild, moderate, severe, critical, and fatal infection, respectively; 42 (63.7%) were hospitalized. Overall, 14, 38 and 14 infections were observed during the 1st (Feb-Jun 2020), 2nd (Jul 2020-Jun2021) and 3rd (Jul 2021-Jan 2022) wave of the pandemic, with an overall incidence rate of 10.2 per 100 pt-yrs. Incidence rates in the 3 waves were 8, 10.2 and 7 per 100 pt-yrs respectively. Hospitalized cases were significantly less frequent during the 3rd wave (35.7% vs 64.3%/73.7% in the 1st/2nd wave, p=0.04). Overall, 283/390 evaluable pts (72.6%) received ≥1 dose of Comirnaty vaccine (19/66 COVID-19 pts; 5, 7 and 7 pts had received 1, 2 or 3 vaccine doses, respectively). At COVID-19 diagnosis, RUX was reduced in 10 (15.1%) pts and discontinued in 9 (13.6%) pts, comparably in MF and PV. In the total cohort, COVID-19 infection was more frequent in pts with MF (15.3% vs. 8.2% PV pts, p=0.04), with ≥1 comorbidity (15% vs. 8.7%, p=0.04). Also, COVID-19 infections after vaccine availability were more frequent in unvaccinated pts (37.4 vs. 6.3%, p<0.001). COVID-19 requiring hospitalization was more frequently observed in pts ≥70 yrs (12.2% vs. 6.8% in pts <70 yrs, p=0.04), and without COVID-19 vaccine (32.4% vs. 2.9%, p<0.001). No additional predictors for COVID-19 were noted analyzing MF and PV separately. In COVID-19 pts, hospitalized cases had a significantly lower median platelet count (275 vs. 168 x109/L, p=0.02), were receiving lower RUX doses (33.3% <10 mg BID vs. 8.3%, p=0.02) and more frequently presented comorbidities (40.5% vs. 13.6%, p=0.03) compared to outpatients. MF vs. PV, median hemoglobin levels, age≥70 yrs and sex were not associated with hospitalization. MF pts who were not in spleen response at COVID-19 infection had higher risk of hospitalization (73% vs. 44.4% in responders, p=0.04). After multivariable Cox analysis including previous anti-SARS-Cov-2 vaccine, need for hospitalization, age≥70 and male sex, OS to COVID-19 was significantly improved in pts who had previously received anti-SARS-Cov-2 vaccine (HR=0.10, p=0.02) (Fig.1), in pts with COVID-19 not requiring hospitalization (HR=0.19, p=0.03) and in patients <70 yrs (HR=0.38, p=0.03). The COVID-19 wave did not impact OS (p=0.53). Image:Summary/Conclusion: Among RUX-treated pts, lower RUX doses, comorbidities and no spleen response are significant predictors of hospitalization. Vaccine was the most protective factor against COVID-19 disease, hospitalization, and mortality. RUX-treated pts, regardless of MPN type, should be sensitized to adherence to the vaccine program and prioritized for antiviral therapy in case of infection.